SAR and optimization of thiazole analogs as potent stearoyl-CoA desaturase inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 20, Issue 5, 2010, Pages 1593-1597

  Ramtohul, Yeeman K ^a   Black, Cameron ^a   Chan, Chi Chung ^a   Crane, Sheldon ^a   Guay, Jocelyne ^a   Guiral, Sébastien ^a   Huang, Zheng ^a   Oballa, Renata ^a   Xu, Li Jing ^a   Zhang, Lei ^a   Li, Chun Sing ^a  

^a MERCK FROSST CENTRE FOR THERAPEUTIC RESEARCH   (Canada)

Author keywords

Body weight gain prevention; Desaturation index; Insulin and glucose sensitivity; SCD inhibitors

Indexed keywords

ACYL COENZYME A DESATURASE; ENZYME INHIBITOR; GLUCOSE; INSULIN; MF 152; PIPERAZINE DERIVATIVE; STEAROYL COA DESATURASE INHIBITOR; THIAZOLE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ARTICLE; CELL LINE; CONTROLLED STUDY; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG DISTRIBUTION; DRUG EFFICACY; DRUG POTENCY; ENZYME ACTIVITY; GLUCOSE BLOOD LEVEL; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; INSULIN BLOOD LEVEL; LIPID DIET; METABOLIC DISORDER; METABOLIC PARAMETERS; MOUSE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OBESITY; STRUCTURE ACTIVITY RELATION; WEIGHT GAIN;

ADMINISTRATION, ORAL; ANIMALS; DIETARY FATS; ENZYME INHIBITORS; HEP G2 CELLS; HUMANS; HYPOGLYCEMIC AGENTS; MICE; MICE, INBRED C57BL; OXADIAZOLES; STEAROYL-COA DESATURASE; STRUCTURE-ACTIVITY RELATIONSHIP; THIAZOLES; WEIGHT GAIN;

MUS;

EID: 76649106722     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2010.01.083     Document Type: Article

References (27)

1. Enoch H.G., Catala A., and Strittmatter P. J. Biol. Chem. 251 (1976) 5095
2. Ntambi J.M. Prog. Lipid Res. 34 (1995) 139
3. Miyazaki M., Kim Y.-C., Gray-Keller M.P., and Attie A.D. J. Biol. Chem. 275 (2000) 30132
4. Ntambi J.M., Miyazaki M., Stoehr J.P., Lan H., Kendziorski C.M., Yandell B.S., Song Y., Cohn P., Friedman J.M., and Attie A.D. Proc. Natl. Acad. Sci. U.S.A. 99 (2002) 11482
5. Jiang G., Li Z., Liu F., Ellsworth K., Dallas-Yang Q., Wu M., Ronan J., Esau C., Murphy C., Szalkowski D., Bergeron R., Doebber T., and Zhang B.B. J. Clin. Invest. 115 (2005) 1030
6. Gutierrez-Juarez R., Pocai A., Mulas C., Ono H., Bhanot S., Monia B.P., and Rossetti L. J. Clin. Invest. 116 (2006) 1686
7. Liu, G.; Zhao, H.; Serby, M. D.; Smith, H. T.; Cao, N.; Surowy, T. K.; Adler, A.; Mika, A.; Farb, T. B.; Keegan, C.; Landschulz, K.; Brune, M.; Collins, C. A.; Sham, H. L.; Camp, H. S. The 233rd ACS National Meeting, Chicago, IL, March 25-29, 2007. Abstract: MEDI 232.
8. Zhao H., Serby M.D., Smith H.T., Cao N., Suhar T.S., Surowy T.K., Camp H.S., Collins C.A., Sham H.L., and Liu G. Bioorg. Med. Chem. Lett. 17 (2007) 3388
9. Liu G., Lynch J.K., Freeman J., Liu B., Xin Z., Zhao H., Serby M.D., Kym P.R., Suhar T.S., Smith H.T., Cao N., Yang R., Janis R.S., Krauser J.A., Cepa S.P., Beno D.W., Sham H.L., Collins C.A., Surowy T.K., and Camp H.S. J. Med. Chem. 50 (2007) 3086
10. Xin Z., Zhao H., Serby M.D., Liu B., Liu M., Szczepankiewicz B.G., Nelson L.T., Smith H.T., Suhar T.S., Janis R.S., Cao N., Camp H.S., Collins C.A., Sham H.L., Surowy T.K., and Liu G. Bioorg. Med. Chem. Lett. 18 (2008) 4298
11. Winther, M. D. 2nd Annual Drug Development for Diabetes and Obesity, London, UK, Jan 17-18, 2008.
12. Koltun D.O., Vasilevich N.I., Parkhill E.Q., Glushkov A.I., Zilbershtein T.M., Mayboroda E.I., Boze M.A., Cole A.G., Henderson I., Zautke N.A., Brunn S.A., Chu N., Hao J., Mollova N., Leung K., Chisholm J.W., and Zablocki J. Bioorg. Med. Chem. Lett. 19 (2009) 3050
13. Koltun D.O., Zilbershtein T.M., Migulin V.A., Vasilevich N.I., Parkhill E.Q., Glushkov A.I., McGregor M.J., Brunn S.A., Chu N., Hao J., Mollova N., Leung K., Chisholm J.W., and Zablocki J. Bioorg. Med. Chem. Lett. 19 (2009) 4070
14. Li C.S., Belair L., Guay J., Murgasva R., Sturkenboom W., Ramtohul Y.K., Zhang L., and Huang Z. Bioorg. Med. Chem. Lett. 19 (2009) 5214
15. Leger S., Black C., Deschenes D., Dolman S., Falgueyret J.-P., Gagnon M., Guiral S., Huang Z., Guay J., Leblanc Y., Li C.-S., Masse F., Oballa R., and Zhang L. Bioorg. Med. Chem. Lett. 20 (2010) 499
16. Uto Y., Ogata T., Harada J., Kiyotsuka Y., Ueno Y., Miyazawa Y., Kurata H., Deguchi T., Watanabe N., Takagi T., Wakimoto S., Okuyama R., Abe M., Kurikawa N., Kawamura S., Yamato M., and Osumi J. Bioorg. Med. Chem. Lett. 19 (2009) 4151
17. Uto Y., Ogata T., Kiyotsuka Y., Miyazawa Y., Ueno Y., Kurata H., Deguchi T., Yamada M., Watanabe N., Takagi T., Wakimoto S., Okuyama R., Konishi M., Kurikawa N., Kono K., and Osumi J. Bioorg. Med. Chem. Lett. 19 (2009) 4159
18. Attie A.D., Krauss R.M., Gray-Keller M.P., Brownlie A., Miyazaki M., Kastelein J.J., Lusis A.J., Stalenhoef A.F., Stoehr J.P., Hayden M.R., and Ntambi J.M. J. Lipid Res. 43 (2002) 1899
19. Hulver M.W., Berggren J.R., Carper M.J., Miyazaki M., Ntambi J.M., Hoffman E.P., Thyfault J.P., Stevens R., Dohm G.L., Houmard J.A., and Muoio D.M. Cell Metab. 2 (2005) 251
20. Nakamura M.T., and Nara T.Y. Annu. Rev. Nutr. 24 (2004) 345
21. Five initial applications from Xenon (WO2005/011653 to WO 2005/011657) were published on February 10, 2005. Representative one: Abreo, M.; Chafeev, M.; Chakka, N.; Chowdhury, S.; Fu, J.-M.; Gschwend, H. W.; Holladay, M. W.; Hou, D.; Kamboj, R.; Kodumuru, V.; Li, W.; Liu, S.; Raina, V.; Sun, S.; Sviridov, S.; Winther, M. D.; Zhang, Z. WO2005/011655.
22. A patent application on five-membered heterocycles was published during the course of this work. However, the examples disclosed are very limited in scope. Kamboj, R.; Zhang, Z.; Fu, J.-M.; Kodumuru, V.; Liu, S.; Sun, S.; Chakka, N. WO2006/034315.
23. For detailed experimental procedures and rat microsomal assay conditions, see: Li, C, S.; Ramtohul, Y.; Huang, Z.; Lachance, N. WO2006/130986.
24. Zhang, L.; Ramtohul, Y.; Gagné, S.; Styhler, A.; Guay, J.; Huang, Z. J. Biomol. Screen., 2010, doi:10.1177/1087057109356208.
25. During the course of this work a publication by Abbott describing some benzylamine and piperidine ether SAR in a six-membered pyrazine ring series was reported, see Ref. 6c.
26. Lachance, N.; Li, C. S.; Leclerc, J.-P.; Ramtohul, Y. K. WO2008/064474.
27. Girardin M., Alsabeh P.G., Lauzon S., Dolman S.J., Ouellet S.G., and Hughes G. Org. Lett. 11 (2009) 1159